The U.S. Food and Drug Administration said it would require stronger safety language on labels of long-acting and extended-release opioids in response to an epidemic of overdoses and deaths from the widely-used pain medicines.

The FDA will highlight on labels the dangers of abuse and possible death, as well as risks to newborns of mothers taking the medicines, it said in a release on Tuesday.

The agency will require extra studies of the drugs to assess known risks of abuse, overdose and death.

FDA Officials noted the number of fatalities from the powerful pills has have more than tripled over the past decade. In a conference call, officials said opioids have played a “disproportionate role” in drug abuse and deaths.

The FDA said the drug labels currently are indicated for patients with moderate to severe pain and would in future indicate they should only be used for severe pain.

Updated language in the drug labels will stress the medicines are meant for pain severe enough to require daily, round the clock, long-term opioid treatment, and only for those who have not had adequate pain relief from alternative medicines.

The labels, when given final approval, will also include prominent boxed warnings that chronic maternal use of the drugs can result in potentially fatal opioid withdrawal syndrome in newborns.

‘These potent drugs have harmed too many patients and devastated too many families and communities’

“The FDA is invoking its authority to require safety labeling changes and postmarket studies to combat the misuse, abuse, addiction, overdose and death from these potent drugs that have harmed too many patients and devastated too many families and communities,” FDA Commissioner Margaret Hamburg said in a release.

The agency said the changes to language in package insert labels for the drugs, when final, will better enable doctors to tailor use of the potentially addictive medicines to individual patients.

If you are experiencing back pain, visiting the doctor might actually make things worse, not better.

A study published online in JAMA Internal Medicine found that instead of a less invasive approach that’s long been recommended, doctors are increasingly responding to patients who report back pain with unnecessary MRIs and other scans, strong painkillers and referrals to specialists.

The study was led by Dr. John N. Mafi of Boston’s Beth Israel Deaconess Medical Center and looked at 23,918 doctor visit records from January 1999 to December 2010. This research has important implications because one in 10 of doctor visits in the U.S. are because of pain in a patient’s lower back.

“The guidelines have been pretty consistent since the 1990s,” says Mafi, the lead author of the study. “The basic approach is ‘less is more’ for patients with routine back pain.”

The results of the study show an increase in the prescription of painkillers such as OxyContin, which is an opioid and therefore does little for mild back pain and nothing for more serious pain. As opioid use increased from 19% to 29% of cases, the use of painkillers that can be purchased over-the-counter decreased from 37% to 25%.

Opioid use can be dangerous: The study discovered that 43% of those using the drugs because of back pain were also suffering from substance abuse problems. Prescribing these can have serious implications. Almost 15,000 fatalities occurred in 2008 due to narcotic use, a number that was greater than cocaine and heroin-related deaths.

Another finding was that rates of MRI and CT scans increased from 7% to 11%. Although these are non-invasive procedures, each scan costs $1,000 or more. Mafi explains patient pressure as the reason for this rush to scan, as patients wish to feel as if their doctor heard their concerns and is giving them a proper check-up.

“We are a society that demands instant solutions, but back pain doesn’t play by these rules,” Mafi says. “Unfortunately, the fancier treatments haven’t been shown to decrease patient’s pain or increase their quality of life.”

Patients without red flags raised such as fever, cancer history, neurologic symptoms or weight loss can and should be treated for lower back pain without strong painkillers or imaging tests, Mafi told JAMA’s in-house blog.

“[That means] use of nonsteroidal anti-inflammatory drugs or acetaminophen and, when pain doesn’t resolve within a couple months, physical therapy. Most cases of new-onset back pain will resolve within a few months.”

TORONTO — Health Canada says children under the age of 12 should not be given codeine-based medication.

That means prescription pain drugs and cough syrups containing codeine should not be used in this age group.

The department says the decision is based on the fact that serious side effects and deaths have occurred in children who have taken codeine drugs or in babies who get codeine through breast milk.

Health Canada says the events are very rare.

The body converts codeine into morphine, but in some people that process happens very quickly; they are called ultra-rapid metabolizers.

Because they convert the drug so quickly, these people can actually have an unexpected overdose of morphine.

As well, there are other serious side-effects seen in children taking codeine, Health Canada says. For instance, surgery to remove tonsils may increase the risk of known codeine side-effects such as the slowing of breathing.

Symptoms of a toxic reaction to codeine or other opioid drugs include dizziness, confusion, extreme sleepiness, or sudden shortness of breath or difficulty breathing.

Health-care professionals and consumers should seek alternatives to codeine for the management of mild to moderate pain or cough in children less than 12 years of age.

In 2008, Health Canada informed health-care professionals and the public of the risk to nursing infants whose mothers are ultra-rapid metabolizers of codeine. At the time, the drug labels of prescription and non-prescription products containing codeine were updated to highlight this risk.

In addition, the labelling advises caution regarding the use of codeine in any patients with breathing conditions, including children.

Health Canada says non-prescription products containing codeine are already labelled to make it clear they should not be used by children.

LONDON — Millions of arthritis sufferers could be increasing their risk of a heart attack or stroke by more than a third by taking large doses of drugs such as ibuprofen, according to one of the largest studies into painkillers.

The study of more than 350,000 patients taking prescription doses of such medications found the chance of a heart attack or stroke rose by almost 40%.

The research found that the greater risk of cardiac side-effects from ibuprofen was similar to those of another arthritis drug, Vioxx, which was withdrawn from the market almost a decade ago when research suggested it might double the risk of heart attacks.

The painkillers were also found to double the risk of heart failure and bleeding ulcers when taken in high quantities

The painkillers, which are known as non-steroidal anti-inflammatory drugs (NSAIDs) and taken by millions of arthritis sufferers each day, were also found to double the risk of heart failure and complications such as bleeding ulcers when taken in high quantities.

The authors of the University of Oxford study said that their findings showed that prolonged use of such medicines was “risky”, but added that patients needed to weigh up the benefits against the potential dangers.

More than seven million people in Britain suffer from rheumatoid arthritis and osteoarthritis, and many rely on high doses of NSAIDs, which are also sold in lower quantities over the counter for common ailments.

The study, published in The Lancet, found that for every 1,000 people with a moderate risk of heart disease, about eight would normally have a heart attack or stroke each year.

When similar patients were given a year of treatment with a high dose of ibuprofen (2,400 milligrams daily) or another NSAID called diclofenac (150mg daily), that risk rose, with 11 patients suffering major cardiac events.

One in three of the extra heart attacks was fatal, the study found.

The same dosage, which is the maximum normally prescribed and twice the amount allowed over the counter, more than doubled the risk of heart failure from three cases in 1,000 to seven, and more than doubled the risks of complications such as bleeding ulcers.

If all seven million people with arthritis took the highest dosage of drugs, it would equate to an estimated 21,000 more heart attacks in sufferers, the study suggested.

‘We are trying to say yes, these drugs are risky, but it may be worth it’

Researchers said the study, funded by the Medical Research Council and the British Heart Foundation and led by the council’s unit at Oxford, had looked at the risks from common painkillers in “unprecedented detail.”

The lead author, Colin Baigent from the University of Oxford, said: “The research shows that, when used in high doses, diclofenac and ibuprofen increase the risk of cardiovascular disease, on average causing about three extra heart attacks a year in every 1,000 patients treated, one of which would be fatal.”

He added: “For many people who take these drugs for severe arthritis they make the difference between being able to go about their daily life or not. We are trying to say yes, they are risky, but it may be worth it.”

The findings, from an analysis of 639 randomized trials, found that a third drug, called naproxen, did not increase the risk of heart attacks or strokes when a high dose of 1,000mg a day was taken.

The study found that it was the most likely of the medications to cause bleeding from the stomach, but researchers said such problems were normally less serious.

Researchers said the cardiac risks from ibuprofen and diclofenac were “mainly relevant” to people with arthritis who were prescribed high doses or long periods. “A short course of lower dose tablets purchased without a prescription, for example, for a muscle sprain, is not likely to be hazardous,” said Prof Baigent.

Last year almost 17 million prescriptions were written by doctors in England for NSAIDs. About a third were for ibuprofen, a third for diclofenac and about a sixth for naproxen.

Alan Silman, the medical director of Arthritis Research UK, urged arthritis sufferers not to be “unduly concerned,” but said family doctors were turning increasingly to naproxen because of the potential cardiac risks of the other medications. He said: “There is an urgent need to find alternatives that are as effective, but safer.”

Dr. Shannon Amoils, research advisor at the BHF, said: “People should take the lowest effective dose of these drugs for the shortest time necessary.”

A new study indicating overdose deaths have risen in close parallel with the country’s soaring consumption of prescription narcotics is more evidence the painkillers have become Canada’s most dangerous drugs after tobacco and alcohol — and need concerted, national action, says a leading addiction researcher.

“We’re giving them to quite a number of people who don’t really need them that urgently,” said Benedikt Fischer of Simon Fraser University. “There is a reason why other, highly developed industrialized nations from the G8 survive and seem to have rather healthy populations — with 25% or 30% of the amount of opioids as we dispense.”

Prof. Fischer and his colleagues suggest in another new study that one in six teenagers use pills like oxycodone and Percocet “non-medically,” yet lawmakers are still not taking the issue seriously enough, Prof. Fischer argued. That just-published research comes on the heels of a third Canadian study released this week, pointing to a link between serious car crashes and taking even low doses of opioids.

This country is second only to the U.S. in per-capita consumption of the drugs. Provincial governments and medical regulators have tried to curb abuse of opioids recently, with measures such as electronic monitoring of prescriptions, while most government drug plans are ending coverage of OxyContin and its tamper-resistant replacement. Those policies are piecemeal, however, and have likely had limited impact, said Prof. Fischer.

Canada needs a comprehensive plan that curbs inappropriate prescribing of the drugs and educates patients about their dangers, he said.

Yet some physicians see a different problem: many Canadians with severe, chronic pain going untreated. Dr. Roman Jovey, a prominent Ontario-based pain specialist, questioned the significance of the new research, and warned against rash action.

Most of the overdoses documented in one of Prof. Fischer’s studies are likely of people who abused opioids — probably along with other drugs that would make the cause of death questionable, said Dr. Jovey.

It’s a tragedy when anybody dies using a prescription, but let’s keep the big picture in mind here

“It’s a tragedy when anybody dies using a prescription, but let’s keep the big picture in mind here,” he said. “Who’s dying?… Is it innocent people — they’re just using the drug like their doctor told them to and they die? I would suggest that’s extremely rare.”

Dr. Jovey, who receives consulting and speaking fees from the maker of OxyContin and other drug firms, argued for balanced solutions, such as better communication and monitoring around opioid use.

Canada rose from sixth to second-largest prescription-opioid consumer in the world over the last decade, with sales reaching $768-million in 2011, according to IMS-Brogan, a market research firm. Meanwhile, evidence points to a rising toll of addiction and overdose death, both among drug addicts and those prescribed by a doctor.

An expert advisory council set up by the federally funded Canadian Centre on Substance Abuse is planning to release a prescription-drug-abuse strategy this March.

The recommendations will strive to ensure cancer patients and others who truly benefit from the drugs can access them, while lessening prescription to people who could be treated in other ways, said Michel Perron, the centre’s CEO. “Everybody would agree that the status quo cannot carry on,” he said.

We still have a pervasive sense amongst patients that they are entitled to their opioids

One of the two new studies compared coroners’ statistics on deaths related to use of four opioids in Ontario and B.C., and levels of consumption of the same drugs from 2005 to 2009.

In Ontario, the number of fatalities linked to Fentanyl, a highly potent painkiller usually delivered through a time-release patch, climbed from 34 to 57, while those for oxycodone, the active ingredient in OxyContin and its replacement OxyNeo, jumped from 96 to 143. The number of oxycodone-related deaths leapt to 173 in 2010, and 166 last year, the chief coroner’s office said this week.

In B.C., overdose deaths related to hydromorphone, commonly known by the brand name Dilaudid, almost tripled to 20 from seven, while oxycodone fatalities ballooned three-fold, to over 30.

In each case, the deaths increased or shrunk in almost perfect unison with the amount of the drugs consumed, noted Prof. Fischer.

Still, Dr. Jovey said, evidence from other jurisdictions suggests that most of those deaths were likely among addicts using the drugs illicitly, while the actual death rates are relatively small — about 30 times less, for instance, than for suicide.

Dr. David Juurlink, co-author of the study on road crashes and opioids with Tara Gomes of Toronto’s Institute for Clinical Evaluative Sciences, argued the problem is serious, and not shrinking in the face of recent regulatory measures.

“We still have a pervasive sense amongst patients that they are entitled to their opioids, they need their opioids, and we have doctors, including some very prominent ones, arguing that is the case,” he said. “Doctors do all kinds of things that are not supported by great evidence … but we do very few things as dangerous as this.”

Hundreds of people across Canada are dying every year from overdoses involving OxyContin, newly divulged coroners-office figures indicate, underlining the toll taken by the country’s epidemic of narcotic-painkiller dependency.

“I would say it’s one of our biggest silent killers right now,” said Deborah Cumming of the Canadian Centre on Substance Abuse. “It’s a legal substance that serves a great purpose … but now we’re seeing this diversion, we’re seeing this abuse and misuse, so what do we do? It’s very politically sensitive.”

Related

Despite a persistent popular image, not all buy the medication illicitly on the street, extracting the active ingredient before snorting or injecting it — a sub-culture fuelled in part by bikers and other criminals. Significant numbers have become hooked while taking prescribed drugs for legitimate pain problems, experts say, and an ill-fated few have overdosed under a doctor’s care, as excessive quantities coursed through their veins.

The Ontario government recently joined a handful of other provinces in implementing a system to closely monitor prescription of opioids, with the hope of at least detecting addicted patients who obtain drugs from multiple doctors.

Ontario has previously revealed that the number of its residents succumbing to OxyContin-related overdoses soared from 35 in 2002 to 143 in 2009, more people than drown every year, and about equal to those killed by HIV, said Dr. Andrew McCallum, Ontario’s chief coroner.

Total yearly deaths from abuse of all prescription opioids have risen to 350, the same number who lose their lives in road accidents.

Few other provinces have parsed out such data, but the National Post obtained figures from three jurisdictions’ coroners.

In B.C., deaths tied to oxycodone tripled to 37 from 2004 to 2009. New Brunswick saw between three and 10 overdose deaths a year attributed to oxycodone, or that drug and others, between 2005 and 2009. Nova Scotia had at least six and up to 11 solely oxycodone-related deaths a year from 2007-2010 and as many as 48 attributed generally to opioids, including oxycodone.

That translates into more than 250 deaths related at least in part to the drug in the four provinces in 2009, the most recent year for which all have statistics.

The victims include Janice Stoltz, an Edmonton pediatric nurse first prescribed OxyContin in the late 1990s for the nagging pain of fibromyalgia. Over the next few years, she seemed to become increasingly dependent on the medication, often sinking into a “fog” under its influence, her daughter, Dana Dmytro, recalls.

In 2002, the 40-year-old single mother was found dead next to her bed, a coroner’s report later saying her breathing had been brought to a halt by the high levels of OxyContin, less-potent codeine and two anti-anxiety drugs in her bloodstream. The autopsy also found five undigested, 80 mg. OxyContin pills in her body.

“It is absolutely the worst tragedy possible,” says Ms. Dmytro, a plaintiff in a class-action lawsuit against Purdue, who described her mother as a normally smart and independent woman. “She became an unrecognizable person who was not my Mom any more, and then she died.”

The addiction and fatal accidents have arisen against the backdrop of Canada’s growing love affair with prescription opioids — natural or synthetic opium-like drugs that provide unparalleled pain relief, but also can be powerfully habit forming.

Canada was second in the world only to the U.S. in its consumption of the medications from 2007 and 2009, ingesting three times the volume used in the United Kingdom and 20 times that consumed in Japan, according to the International Narcotic Control Board.

Yet pain-treatment specialists argue that, despite the widespread problems, millions of Canadians are still going untreated for chronic, non-cancer pain. If doctors carefully screen out patients with addiction potential and supervise people closely, medications like OxyContin can be a godsend for those coping with chronic pain from conditions like diabetes or arthritis, or recovering from injuries or surgery, they say.

“Chronic non-cancer pain is a huge problem in Canada,” said Dr. Brian Goldman, a pain expert at Toronto’s Mount Sinai Hospital. Some in the field worry that further restricting the prescription of opioids would only create a chill among doctors, depriving patients who truly need help.

Still, the dangers of the drugs are hard to ignore. Breakaway Addiction Services in Toronto has seen a “huge” spike in clients hooked on OxyContin and other prescription opioids lately, including people “from every class, every nationality, every income bracket, every professional group,” said Bob Martel, a clinic manager.

For many, the habit starts after being prescribed the “highly addictive” drug to treat pain from a work injury or operation, though many clients have underlying emotional troubles as well, he said.

“For some people it not only relieves physical pain, I think it relieves their psychic pain or spiritual pain,” said Mr. Martel. “It just flattens you out, and everything is all right.”

Ontario addiction programs saw the number of prescription-opioid cases rise steadily in the late 1990s, a study reported last year, and it seems the upward trend has continued since. The number of calls to Ontario’s drug and alcohol help line about narcotic painkillers — mostly OxyContin — climbed to 4,700 in the year that ended last month, up from 2,700 in 2008-09, according to ConnexOntario, which runs the line for the provincial government. Opioid calls now outnumber cocaine, at 4,400.

It was a pleasant, informative break from the grind for a crowd of local doctors: lunch and a series of lectures at Vancouver’s chic Four Seasons Hotel, all presented free by Purdue Pharma, which had just rolled out a new pain drug called OxyContin.

The specialists Purdue paid to speak at the 1997 forum, including Toronto’s Dr. Brian Goldman, who now hosts a popular CBC-Radio show, encouraged doctors to overcome fear of such “opioid” medicines and consider them even for patients with chronic non-cancer pain.

Similar, Purdue-sponsored talks were held across the country in the following months and years, while sales reps fanned out to visit family doctors and others, promoting the drug’s continuous-release convenience and its supposedly low potential for abuse.

Related

While opioids had long been reserved primarily for terminal cancer patients, ads in medical journals touted OxyContin — with up to twice the potency of morphine — as a safer alternative to even Aspirin and Tylenol and good for anyone who needed pain relief for “several days” or more.

It was not long before OxyContin was being widely prescribed in the Vancouver area, notes Dr. Thomas Perry, a local physician-pharmacologist, in an affidavit filed in a Nova Scoita class-action lawsuit against Purdue. Sales accelerated across the country, soaring from $3-million in 1998 to $243-million last year, according to IMS-Brogan, which tracks drug trends.

“The biggest surprise for us in Canada at the time was how fast it took off,” said Dwain May, a former Purdue executive in Alberta.

“This campaign was amazingly successful,” said Dr. Mel Kahan, a University of Toronto addiction expert. “It was probably the most successful marketing campaign in history as far as I know for any class of drug.”

What happened next is now common knowledge, though the full extent of the “Hillbilly heroin’s” dark side has only recently become apparent. Addiction to the “low-abuse” drug — and other, similar opioid painkillers — has reached near-epidemic proportions, with 140 people a year in Ontario alone dying from overdoses related to the drug, more than are killed in drowning mishaps, according to the province’s coroner. Victims include street users, people taking what their doctor prescribed and those getting OxyContin from both legal and underground sources.

Less discussed has been the role of Purdue’s own, highly effective marketing in Canada. Driving home the message directly and indirectly that OxyContin could be used safely for a broad range of patients, it is at least partly to blame for the scourge of addiction and death, critics allege.

David Hartley/Bloomberg News

Physicians agree the drug has tremendous benefit for the right patient — carefully screened for addictive tendencies and closely monitored — but as a powerful narcotic it has the potential for triggering abuse and respiratory troubles that have killed even some patients taking it as their doctor prescribed, coroners reports show.

A National Post investigation has catalogued a host of Canadian promotional tactics for OxyContin that some experts say are difficult to justify. They range from allegedly misleading claims by sales reps and medical-journal ads to the thousands spent on a textbook, website and presentations by paid experts that encouraged more liberal prescribing of opioids, based on debatable evidence.

“The overall impression that physicians have been left with is that these drugs are very effective and very safe,” said Dr. Irfan Dhalla, a University of Toronto family-medicine professor who has studied the issue extensively. “And that is simply not true.”

OxyContin may be no more addictive than other opioids; aggressive marketing, though, exposed a potent opioid to an unprecedented number of Canadians, making the ensuing problems almost inevitable, he said.

The company, however, says that its promotion has always stuck to the letter of the law and to claims approved for OxyContin by Health Canada, and notes it has been heavily involved in efforts to combat the “diversion” of its drug from legal consumption to the street. That includes supplying prescription-drug abuse brochures to police, and supporting research on opioid addiction.

Some analysts, in fact, blame the troubles on organized-crime groups and the massive profits they earn on OxyContin trafficking, while the decision by several provinces to cover the cost of the pills under public drug plans also helped spread their use significantly.

What’s more, the company’s concerns about misuse have prompted it to decide to replace OxyContin next year with a new version of the drug, said Randy Steffan, Purdue’s corporate affairs director. OxyNEO has been specially hardened to reduce the risk of it being crushed or otherwise modified by addicts to release the active ingredient, he said.

“The addiction to OxyContin … is a complex societal problem,” said Dr. Pat Morley-Forster, a University of Western Ontario pain specialist whose clinic is partly funded by Purdue. “I don’t think any one organization or institution can be held responsible, any more than saying that the marketing of automobiles or Tim Hortons is responsible for the rise in obesity and diabetes.”

Yet in 2007, the company’s U.S. branch did, in fact, plead guilty to “misbranding” the drug to physicians and agreed to a settlement with the federal government of $635-million, admitting to various fraudulent marketing methods in one of the States’ biggest-ever prosecutions of a drug firm.

A handful of class-action lawsuits alleging similar transgressions in Canada have been launched, partly overseen by Halifax lawyer Ray Wagner; Purdue has yet to file any statements of defence. Government authorities here, though, say they see no reason to take action.

Health Canada has never received complaints about Purdue’s marketing of OxyContin, nor heard concerns from the Pharmaceutical Advertising Advisory Board — a non-government body that reviews promotional material submitted voluntarily by firms — and has not investigated the company, said Olivia Caron, a department spokeswoman.

Purdue Canada operates independently of the U.S. branch and its marketing efforts are governed by distinct laws here, said Mr. Steffan.

Direct promotion of OxyContin by reps and in advertising ended in 2007, he said, though Purdue-funded expert talks and articles discussing the value of opioid treatment continue to this day.

“We were really trying to be quite careful,” recalled Mr. May, the former Purdue sales manager. “I still maintain that the messaging was correct, in terms of trying to get the appropriate patient…. These were patients who couldn’t work, who couldn’t function in society and they were looking for a way to control their pain and hopefully get back to work.”

The promotional techniques Purdue employed are in many ways standard practice in the pharmaceutical business, whose interaction with doctors and researchers has long been a subject of hot debate. OxyContin’s dramatic impact, however, brings that relationship into sharp focus.

The product was essentially a new means to deliver an old drug, oxycodone, a semi-synthetic derivative of opium. The pills are designed to release the dose continuously over 12 hours, as well as send an initial burst into the patient’s bloodstream within about 45 minutes. Like other narcotic painkillers, though, an excessive dose, or too much of the drug for someone not accustomed to opioids, can trigger respiratory depression, where breathing can slow to a halt, starving the heart of oxygen and causing cardiac arrest.

Purdue’s patent on another continuous-release narcotic, MS Contin, had just expired when the Pickering, Ont.-based firm switched its marketing attention to OxyContin in 1997. Purdue has a yearly promotional budget of $14-million in Canada for its painkilling products, according to a former executive’s profile on the Linked-In website. As direct-to-consumer advertising of prescription drugs is all but banned here, virtually all those resources are targeted at the country’s physicians, the gatekeepers who make or break any new medication.

They include Brockville’s Dr. Alan Redekopp, who testified at an inquest this summer that his main source of knowledge about OxyContin was the visits Purdue reps paid him every two months from the late-’90s until last November.

“I was told it was a drug of low-abuse potential,” said Dr. Redekopp, who faces disciplinary action over his prescribing of the drug. “That it would not be, at that time, abused by diversion.”

By 2000, it was common knowledge that OxyContin was, in fact, being widely abused; but even then, he said, the sales reps barely changed their message, advising him only to “choose your patients carefully.”

When he asked them in 2007 about safe maximum doses, they responded that specialized pain clinics were prescribing as much as 1,000 mgs “very successfully,” Dr. Redekopp told the inquest. Recently published guidelines suggest a maximum of 200 mgs, unless a specialist is consulted.

He ended up prescribing patient Donna Bertrand 1,400 mgs a day for her back pain. In 2008, surrounded by empty pill bottles in Ms. Bertrand’s apartment, a teenager ingested alcohol and the OxyContin she gave him, passed out and never awoke. The single mother died herself days later, though her overdose was blamed on other medications.

Dr. Henry Chapeskie recalls Purdue reps coming to his office in Thorndale, Ont., northeast of London, with a reassuring message about the new drug. “I don’t remember any of the reps expressing any concerns (about abuse) at all,” he said. “ ‘It’s just a good medication, and you should be using it for your people with chronic pain.’ ”

The salespeople went out of their way to distance themselves from their American colleagues after the U.S. prosecution, Dr. Chapeski recalled. They were “adamant” that “Purdue USA has nothing to do with Purdue Canada.”

Don Healy / Postmedia News files

In Thunder Bay, Ont., Dr. Robert Algie said his Purdue representatives also presented a clear narrative around OxyContin in the years after its launch.

“It was felt to be safe and you could use it without too much concern…. If people had genuine pain, they weren’t likely to get addicted,” recalled Dr. Algie, past president of the Ontario College of Family Physicians. “Those were some of the buzz words we had to deal with. And a lot of us said, ‘OK, that’s fine.’ And some of us are paying the price of having people who are chronically addicted.”

Mr. May, the ex-Purdue manager, argues OxyContin was marketed cautiously and responsibly in Canada, based largely on its continuous-release feature, which meant patients didn’t have to pop pills every couple of hours. Another former employee calls it a great drug, one his own mother has been taking without problems since 2004. Mr. May confirmed, however, that reps did tell doctors initially — before evidence to the contrary emerged — that the drug had low abuse potential because of its special formulation.

In its settlement with the U.S. government, Purdue admitted there never was any good evidence that OxyContin was less addictive than other opioids.

Mr. May also confirmed reps were paid bonuses tied to the number of prescriptions doctors filled for OxyContin, as they were for other Purdue products and is common in the industry. But those incentives account for only about 10% of their income, not enough to motivate them to make rash claims, he said.

In contrast, he said a rival company selling another new opioid product at the same time employed much more aggressive methods, offering free trips to physicians with high prescription numbers and coupons that would allow patients to get their first prescription free.

Purdue management discussed using the coupons for OxyContin but rejected the idea as inappropriate, Mr. May said. More recently, though, the company has issued such patient “vouchers” for a new opioid pain patch, BuTrans, earning a rare rebuke from the pharmaceutical trade association’s ethics appeal tribunal this July.

Meanwhile, the company ran ads in medical publications that depicted OxyContin as a seemingly benign drug with wide application. One published in the Canadian Medical Association Journal — distributed to virtually every doctor in the country — in 2001 shows a photograph of a fit-looking jogger, with the tag line “one to start and stay with.”

It asserts that OxyContin has “no risk of acetaminophen or ASA toxicity,” giving the impression it is generally safer than Tylenol and Aspirin, said Dr. Dhalla. He said he is unaware of any studies showing OxyContin is less dangerous.”

It also depicts what the ad calls an “adapted” version of a World Health Organization ladder-graphic meant to show doctors the escalating strengths of different pain drugs. Unlike the real WHO ladder, it shows oxycodone on the second step and morphine on the third. Yet oxycodone is actually 1.5 to two times more powerful than morphine, notes Dr. Dhalla. And he said the WHO pain ladder is a yardstick for treating cancer patients; the UN body has never recommended opioids for non-malignant pain.

An ad that appeared in the journal in 2003 contained a larger caution about OxyContin’s abuse potential, but again promoted its use to treat relatively short-term pain, featuring a healthy-looking young father leaning on a crutch after an unspecified injury, above the headline “For pain lasting several days or more.”

At the same time, the company was recruiting specialists to educate doctors about pain management, their message about an epidemic of untreated chronic pain conveniently falling in line with the OxyContin campaign, even if speakers — who receive about $2,000 per talk — did not specifically plug the product. A former sales manager for Purdue in Western Canada, who asked not to be named, called them “paid poster boys.”

The Purdue-funded experts included Dr. Goldman, a respected emergency physician and pain expert at Toronto’s Mount Sinai Hospital, well known for hosting White Coat, Black Art, a popular CBC Radio show on health issues. He was one of the speakers at that Vancouver Four Seasons event and others like it and has authored a number of articles for Purdue publications since.

In his 2010 memoir, The Night Shift, he discloses that he began working for an unnamed pharmaceutical company in the late 1990s, doing talks and educational videos funded by “unrestricted” company grants.

“If I travelled to another city to give the talk, it was on the company’s dime,” he wrote. “I was put up in five-star hotels and taken to nice restaurants. When I travelled across the continent, I was invariably given a ticket in business class.”

Dr. Goldman, who also gives talks on opioid addiction, said he believes the companies never had any direct input on the opinions he voiced, which he said he developed before being hired to speak for any manufacturer.

There were some tense moments, though. A manager of an unnamed company berated him for talking positively about a rival’s drug during one presentation, while an interview for a company-sponsored video was interrupted several times as executives tried to elicit what they considered the right answer.

Dr. Goldman said this week, however, that he has stopped doing talks, videos and articles for Purdue and now realizes that any physician who accepts such paid pharmaceutical-company work is “likely to be influenced by that fact.”

Mr. Steffan said Purdue reimburses about 100 Canadian doctors to educational work annually — a number he said grew in recent years because of greater attention being paid to pain management — but the goal is to provide “evidence-based” teachng, governed by the industry’s ethics code.

Don Healy / Postmedia News files

One of them, Dr. Roman Jovey, former president of the Canadian Pain Society, found himself in the midst of an unusual controversy at the University of Toronto last year. Two physicians complained that the Purdue-funded speaker was one of the teachers in the university’s inter-faculty pain-curriculum course, and that students had for years been receiving free copies of Pain Management, a textbook paid for and copyrighted to Purdue. Early versions of the book said continuous-release opioids like OxyContin had low abuse potential; even the latest edition says doctors have an ethical duty to consider opioids for non-cancer patients.

Dr. Philip Berger, head of family medicine at St. Michael’s Hospital, said his reaction was “utter astonishment” when he heard of the company’s involvement in the course. “I’m shaking my head right now,” he said in a recent interview. “The pharmaceutical industry produces a lot of good drugs, but … their only motivation for getting into medical schools is to encourage students who then become doctors to prescribe their products.”

The university took the rare step of moving responsibility for the course from its Centre for the Study of Pain to another unit, while barring industry-linked speakers and ending distribution of the Purdue text.

Purdue’s financial ties to Canada’s community of pain specialists stretch much further, though. Twelve of 49 experts on a panel that produced new practice guidelines on using opioids to treat non-cancer pain last year, for instance, disclosed that they receive speaking or consulting fees of more than $5,000 a year from Purdue or Purdue and other companies.

One advisory-panel member, Western’s Dr. Morley-Forster, revealed that her pain clinic in London has received $200,000 from Purdue. She has long voiced strong views that chronic pain is under-treated and praised OxyContin as a “genuine advance” in treatment in a 2007 op-ed article in the London Free Press.

She defended the grant in an email response to questions, saying the real issue is that the province is providing insufficient funding for clinics that offer a range of both pharmaceutical and non-drug therapies for pain, leaving little choice but to accept industry money. Some clinics are already closing down, said Dr. Morely-Forster.

“This will have the effect of increasing opioid prescribing, ironically, since that is the only modality that doctors can get covered for the patient,” she said.

In fact, evidence suggests that family physicians have been among the biggest prescribers of OxyContin and other opioids, their patients often unable to access over-burdened pain clinics. Some generalists, though, say they are sometimes unsure whether to trust the advice of specialists funded by pharmaceutical manufacturers, while other education is hard to come by.

WASHINGTON — Lethal overdoses from prescription painkillers have tripled in the past decade and now account for more deaths than heroin and cocaine combined, U.S. health authorities said Tuesday.

The quantity of painkillers on the market is so high that it would be enough to medicate every American with a standard dose of Vicodin every four hours for one full month, according to the Centers for Disease Control and Prevention.

“The unfortunate and in fact shocking news is that we are in the midst of an epidemic of prescription drug overdose in this country. It is an epidemic but it can be stopped,” said CDC chief Thomas Frieden.

“In fact, now the burden of dangerous drugs is being created more by a few irresponsible doctors than by drug pushers on street corners.”

The CDC Vital Signs report focused on opioid pain relievers, including oxycodone, methadone and hydrocodone, better known as Vicodin, which have quadrupled in sales to pharmacies, hospitals and doctors’ offices since 1999.

Last year, 12 million Americans reported taking prescription painkillers for recreational uses, not because of a medical condition.

The number of deaths from overdoses of opioid pain relievers has more than tripled from 4,000 people in 1999 to 14,800 people in 2008.

The epidemic is at its height among middle-aged white men and American Indians or Alaska natives, the CDC said.

Rural and poor areas tend to have the highest prescription drug overdose death rates.

Deaths from prescription drugs made up almost 75% of overdose deaths in which a drug was specified on the death certificate, the CDC said, noting that deaths and hospitalizations have increased in parallel with the boost in supply.

The sales rate of the three opioids included in the study reached 7.1 kilograms per 10,000 population last year, or the same as 710 milligrams per person in the United States.

“Enough OPR [opioid pain relievers] were prescribed last year to medicate every American adult with a standard pain treatment dose of five milligrams of hydrocodone [Vicodin and others] taken every four hours for a month,” the CDC said.

Even though a relatively small portion of the US population admits abusing prescription painkillers, the costs to health insurance companies are huge — US$72.5-billion per year, according to the report.

States could do a better job of regulating the problem via drug monitoring records and insurance claims information that “can identify and address inappropriate prescribing and use by patients,” the report said.

More laws targeting so-called “pill mills,” which are prescribing at higher than normal rates in particularly affected states, could also cut back on the problem, it said.

“State policy can make a huge difference in either controlling or allowing this epidemic to proceed,” said Frieden. “States should rigorously monitor who is prescribing and to whom.”

New research has emerged from Europe that suggests a link between taking mild painkillers during pregnancy and cryptorchidism in baby boys – a condition where one or both testicles fail to descend into the scrotum and a known risk factor for poor semen quality and testicular germ cell cancer in later life.

It turns out that the Western world is experiencing an increased problem with male reproduction functions, but it would be risky to say experts have come up with a conclusive reason why. Canada and the United States have the highest country rates of cryptorchidism, according to the International Clearinghouse for Birth Defects.

The researchers from Denmark, Finland and France published their new findings Monday in Europe’s medical journal Human Reproduction.

The study shows that the use of mild painkillers such as paracetamol, aspirin and ibuprofen, may be part of the reason for the increase in male reproductive disorders in recent decades. It concludes that women who used more than one painkiller simultaneously had a seven-fold increased risk of giving birth to sons with some form of cryptorchidism compared to women who took nothing.

The second trimester appeared to a particularly sensitive time. Any painkiller used at this point in the pregnancy more than doubled the risk of cryptorchidism.

The researchers said there has been a marked increase in the incidence of congenital cryptorchidism in Denmark where it has increased from 1.8% in 1959-1961 to 8.5% in 1997-2001.

“The magnitude of this difference is too large to be accounted for by random fluctuations and differences in ascertainment,” they write in their paper.

The impetus for the study was previous research on rats which showed a connection between painkillers and testosterone supply during the crucial period of gestation when male organs were forming.

The researchers also said that if scientists accept previous research that links exposure to chemicals, which are known hormone disruptors, as a cause for male reproductive disorders, then scientists should also be willing to look at how painkillers disrupt hormone production, namely testosterone.

“For women using mild analgesics (painkillers) during the pregnancy, the mild analgesics will be by far the largest exposure to hormone disruptors,” said lead researcher, Dr. Henrik Leffers at Rigshospitalet University Hospital in Copenhagen.

It should be noted that there was a limitation in this study as it relied on self-reporting from pregnant women.

The study looked at two groups of women, 834 in Denmark and 1463 in Finland, who joined the study while they were pregnant. In Finland the women answered written questionnaires about their use of medication during pregnancy and in Denmark the women did the same or took part in a telephone interview, or both.

The researchers found that women significantly under-reported the use of painkillers in the written questionnaire because they did not consider mild painkillers to be medication.